Psychedelics Promote Structural and Functional Neural Plasticity

Bibliographic Data

ID23323653
AuthorsCalvin Ly (University of California, Davis), Alexandra C Greb (0000-0003-0667-1844, University of California, Davis), Lindsay P Cameron (0000-0002-8420-7898, University of California, Davis), Jonathan M Wong (0000-0002-8327-1345, University of California, Davis), Eden V Barragan (0000-0002-8972-9804, University of California, Davis), Paige C Wilson (University of California, Davis), Kyle F Burbach (0000-0002-5086-7409, University of California, Davis), Sina Soltanzadeh Zarandi (University of California, Davis), A Sood (0000-0003-1767-1049, University of California, Davis), Michael R Paddy (University of California, Davis), Whitney C Duim (University of California, Davis), Megan Y Dennis (0000-0002-8502-5420, University of California, Davis), A Kimberley McAllister (0000-0001-9177-9889, University of California, Davis), Kassandra M Ori-McKenney (0000-0003-2051-2495, University of California, Davis), John A Gray (0000-0002-7287-0748, University of California, Davis), David E Olson (0000-0002-4517-0543, University of California, Davis, corresponding author)
Year2018
Volume23
Issue11
Pages3170-3182
Publication date2018-06-01
Peer ReviewedYes
Open AccessYes
TypeARTICLE
VenueCell Reports (JOURNAL)
Journal identifiersISSN: 2211-1247 • E-ISSN: 2639-1856
PublisherElsevier BV (PUBLISHER)
DOI10.1016/j.celrep.2018.05.022
PMID29898390
OpenAlexW2808301300
LanguageEN
Citations received82
References cited107

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.

Antidepressant · Biology · Hippocampus · Neuroplasticity · PI3K/AKT/mTOR pathway · Prefrontal cortex · Signal transduction · Structural plasticity · Cell Biology · Chemical synthesis and alkaloids · Chemistry · Neuroscience · Neurotransmitter Receptor Influence on Behavior · Psychedelics and Drug Studies

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